This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1xon

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:52, 14 February 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1xon.gif|left|200px]]<br /><applet load="1xon" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1xon, resolution 1.72&Aring;" />
 
-
'''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast'''<br />
 
-
==Overview==
+
==Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast==
-
Phosphodiesterases (PDEs) comprise a large family of enzymes that catalyze the hydrolysis of cAMP or cGMP and are implicated in various diseases. We describe the high-resolution crystal structures of the catalytic domains of PDE4B, PDE4D, and PDE5A with ten different inhibitors, including the drug candidates cilomilast and roflumilast, for respiratory diseases. These cocrystal structures reveal a common scheme of inhibitor binding to the PDEs: (i) a hydrophobic clamp formed by highly conserved hydrophobic residues that sandwich the inhibitor in the active site; (ii) hydrogen bonding to an invariant glutamine that controls the orientation of inhibitor binding. A scaffold can be readily identified for any given inhibitor based on the formation of these two types of conserved interactions. These structural insights will enable the design of isoform-selective inhibitors with improved binding affinity and should facilitate the discovery of more potent and selective PDE inhibitors for the treatment of a variety of diseases.
+
<StructureSection load='1xon' size='340' side='right'caption='[[1xon]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1xon]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XON FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PIL:3-(CYCLOPENTYLOXY)-N-(3,5-DICHLOROPYRIDIN-4-YL)-4-METHOXYBENZAMIDE'>PIL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xon OCA], [https://pdbe.org/1xon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xon RCSB], [https://www.ebi.ac.uk/pdbsum/1xon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xon ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xo/1xon_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xon ConSurf].
 +
<div style="clear:both"></div>
-
==Disease==
+
==See Also==
-
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]]
+
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
1XON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=PIL:'>PIL</scene>, <scene name='pdbligand=B3P:'>B3P</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XON OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
Structural basis for the activity of drugs that inhibit phosphodiesterases., Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY, Structure. 2004 Dec;12(12):2233-47. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15576036 15576036]
+
-
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Artis, D R.]]
+
[[Category: Artis DR]]
-
[[Category: Bollag, G.]]
+
[[Category: Bollag G]]
-
[[Category: Card, G L.]]
+
[[Category: Card GL]]
-
[[Category: England, B P.]]
+
[[Category: England BP]]
-
[[Category: Fong, D.]]
+
[[Category: Fong D]]
-
[[Category: Gillette, S.]]
+
[[Category: Gillette S]]
-
[[Category: Ibrahim, P N.]]
+
[[Category: Ibrahim PN]]
-
[[Category: Kim, S H.]]
+
[[Category: Kim S-H]]
-
[[Category: Lee, B.]]
+
[[Category: Lee B]]
-
[[Category: Luu, C.]]
+
[[Category: Luu C]]
-
[[Category: Milburn, M V.]]
+
[[Category: Milburn MV]]
-
[[Category: Powell, B.]]
+
[[Category: Powell B]]
-
[[Category: Schlessinger, J.]]
+
[[Category: Schlessinger J]]
-
[[Category: Suzuki, Y.]]
+
[[Category: Suzuki Y]]
-
[[Category: Tabrizizad, M.]]
+
[[Category: Tabrizizad M]]
-
[[Category: Zhang, K Y.J.]]
+
[[Category: Zhang KYJ]]
-
[[Category: B3P]]
+
-
[[Category: EDO]]
+
-
[[Category: MG]]
+
-
[[Category: PIL]]
+
-
[[Category: ZN]]
+
-
[[Category: pde]]
+
-
[[Category: pde4d]]
+
-
[[Category: phosphodiesterase]]
+
-
[[Category: piclamilast]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:56:59 2008''
+

Current revision

Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast

PDB ID 1xon

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xon"
Personal tools